Sensor apparatus

ABSTRACT

A sensor apparatus capable of measuring an analyte with excellent sensitivity is provided. A sensor apparatus includes an element substrate; a detecting section disposed on an upper surface of the element substrate, the detecting element including a reaction section having an immobilization film to detect an analyte, a first IDT electrode configured to generate an acoustic wave which propagates toward the reaction section, and a second IDT electrode configured to receive the acoustic wave which has passed through the reaction section; and a protective film which covers the first IDT electrode and the second IDT electrode. The element substrate is configured so that a region where the reaction section is located is at a lower level than a region where the first IDT electrode is located and a region where the second IDT electrode is located.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation application of U.S. patentapplication Ser. No. 15/305,761, filed on Oct. 21, 2016 which is acontinuation of International Application No. PCT/JP2015/077877, filedon Sep. 30, 2015, which claims the benefit of Japanese PatentApplication No. 2014-201249, filed on Sep. 30, 2014. The contents ofthese applications are incorporated herein by reference in theirentireties.

TECHNICAL FIELD

The present invention relates to a sensor apparatus which is capable ofmeasurement on the properties or constituents of an analyte liquid.

BACKGROUND ART

There is known a sensor apparatus which measures the properties orconstituents of an analyte liquid by detecting an object to be detectedcontained in the analyte liquid with use of a detecting element such asa surface acoustic wave device (refer to Patent Literatures 1 to 3, forexample).

For example, in a sensor apparatus employing a surface acoustic wavedevice, a reaction section which undergoes reaction with a componentcontained in a sample of an analyte liquid, is disposed on apiezoelectric substrate, and the properties or constituents of theanalyte liquid are detected by measuring variation in a surface acousticwave propagating through the reaction section. Such a measurement methodusing the surface acoustic wave device or the like has the advantageover other measurement methods (for example, enzymatic method) in thatit lends itself to simultaneous detection of a plurality ofcharacteristics to be measured.

However, in such a conventional sensor apparatus, since the reactionsection, which is placed between a pair of IDT electrodes, is notpositioned at a level which is sufficiently low relative to the IDTelectrodes, it follows that surface-acoustic-wave energy cannot bereadily concentrated on the reaction section, which leads todifficulties in detecting an object to be detected contained in theanalyte liquid with high sensitivity.

CITATION LIST Patent Literature

-   Patent Literature 1: Japanese Unexamined Patent Publication JP-A    5-240762 (1993)-   Patent Literature 2: Japanese Unexamined Patent Publication JP-A    2006-184011-   Patent Literature 3: Japanese Unexamined Patent Publication JP-A    2010-239477

SUMMARY OF INVENTION Technical Problem

Thus, there is a demand for a sensor apparatus which is capable ofdetecting an object to be detected contained in an analyte liquid withexcellent sensitivity.

Solution to Problem

A sensor apparatus according to an embodiment of the invention includes:an element substrate; a detecting section disposed on an upper surfaceof the element substrate, the detecting section including a reactionsection having an immobilization film to detect an object to bedetected, a first IDT electrode configured to generate an acoustic wavewhich propagates toward the reaction section, and a second IDT electrodeconfigured to receive the acoustic wave which has passed through thereaction section; and a protective film which covers the first IDTelectrode and the second IDT electrode, wherein the upper surface of theelement substrate is configured so that a region where the reactionsection is located is at a lower level than a region where the first IDTelectrode is located and a region where the second IDT electrode islocated.

Advantageous Effects of Invention

In accordance with the sensor apparatus according to the embodiment ofthe invention, the upper surface of the element substrate is configuredso that the region where the reaction section is located is at a lowerlevel than the region where the first IDT electrode and the second IDTelectrode are located. Therefore, in the reaction section, energy of thesurface acoustic wave propagating between the first IDT electrode andthe second IDT electrode is readily concentrated on the immobilizationfilm, measurement can be carried out with high sensitivity.

BRIEF DESCRIPTION OF DRAWINGS

FIGS. 1A to 1C are views showing a sensor apparatus according to anembodiment of the invention, and FIG. 1A is a plan view, FIG. 1B is alengthwise sectional view, and FIG. 1C is a widthwise sectional view;

FIGS. 2A to 2E are exploded plan views of the sensor apparatus shown inFIGS. 1A to 1C;

FIGS. 3A to 3E are plan views showing procedural steps to manufacturethe sensor apparatus shown in FIGS. 1A to 1C;

FIG. 4 is a plan view showing a detecting element of the sensorapparatus shown in FIGS. 1A to 1C;

FIGS. 5A and 5B are sectional views showing the detecting element of thesensor apparatus shown in FIGS. 1A to 1C;

FIGS. 6A and 6B are enlarged sectional views showing part of the sensorapparatus shown in FIGS. 5A and 5B; and

FIGS. 7A to 7J are schematic views showing procedural steps tomanufacture the detecting element 3.

DESCRIPTION OF EMBODIMENTS

Hereinafter, embodiments of a sensor apparatus according to theinvention will be described with reference to drawings. In each drawingto be referred to in the following description, like constituent membersare identified with the same reference symbols. Moreover, for example,the size of each member and the distance between the individual membersare schematically shown in each drawing and may therefore differ fromthe actual measurements.

<Structure of Sensor Apparatus>

A sensor apparatus 100 according to an embodiment of the invention willbe described with reference to FIGS. 1A to 6B. As shown in FIGS. 1A to1C, the sensor apparatus 100 according to the embodiment mainlycomprises a first cover member 1, an intermediate cover member 1A, asecond cover member 2, and a detecting element 3.

Specifically, as shown in FIG. 1B, the sensor apparatus 100 has an inletport 14 for admission of an analyte liquid, and a flow channel 15 whichis in communication with the inlet port 14, is surrounded by theintermediate cover member 1A and the second cover member 2, and extendsat least to a reaction section 13. In this embodiment, the intermediatecover member 1A and the second cover member 2 are greater in width thanthe detecting element 3. This allows an analyte liquid to flow so as tocover the entire surface of the detecting element 3 effectively.

FIG. 1C which shows sectional views of the construction shown in FIG.1A, wherein there are successively shown, in top-to-bottom order, asection taken along the line a-a, a section taken along the line b-b,and a section taken along the line c-c. The inlet port 14 is formed soas to pass through the second cover member 2 in a thickness directionthereof.

(First Cover Member 1)

As shown in FIGS. 1A, 1B and FIG. 2A, the first cover member 1 is shapedlike a flat plate. The thickness of the first cover member 1 falls inthe range of 0.1 mm to 1.5 mm, for example. The first cover member 1 hassubstantially a rectangular planar configuration. The longitudinallength of the first cover member 1 falls in the range of 1 cm to 8 cm,for example, and, the widthwise length of the first cover member 1 fallsin the range of 1 cm to 3 cm, for example.

As the material for forming the first cover member 1, for example, aglass-epoxy material, paper, plastics, celluloid, ceramics, non-wovenfabric, and glass can be used. The use of plastics is desirable from thestandpoints of required strength and cost.

Moreover, as shown in FIGS. 1A and 2A, on the upper surface of the firstcover member 1 are formed a terminal 6 and a wiring line 7 routed fromthe terminal 6 to a position near the detecting element 3.

The terminal 6 is formed on either side of the detecting element 3 in awidth direction on the upper surface of the intermediate cover member1A. Specifically, at least part of the terminals 6 arranged relative tothe detecting element 3 lies closer to the inlet port 14 than an inletport 14-side end of the detecting element 3. Moreover, in the range offour terminals 6 placed in an array on one side of the detecting element3 with respect to a direction longitudinally of the flow channel 15, thewiring lines 7 connected to two outer terminals 6, respectively, havesubstantially the same length, and, the wiring lines 7 connected to theother two inner terminals 6, respectively, have substantially the samelength. This makes it possible to reduce variations in signals obtainedby the detecting element 3 resulting from the difference in lengthbetween the wiring lines 7. In this case, with a construction in whichthe wiring lines 7 are connected so that a potential difference occursbetween grounding (earthing) wiring, which is constituted by one pair ofthe wiring lines 7 having substantially the same length, and signalwiring, which is constituted by the other pair of the wiring lines 7having substantially the same length, for example, upon application of apredetermined voltage from external measurement equipment to a first IDTelectrode 11 as shown in FIG. 4 via the wiring line 7, a firstextraction electrode 19, and so forth, it is possible to reduce thesignal variations, and thereby achieve an improvement in detectionreliability.

When measurement is made on the sensor apparatus 100 with externalmeasuring equipment (not shown in the drawing), the terminal 6 and theexternal measuring equipment are electrically connected to each other.Moreover, the terminal 6 and the detecting element 3 are electricallyconnected to each other via the wiring line 7, for example.

A signal issued from the external measuring equipment is inputted to thesensor apparatus 100 via the terminal 6, and, a signal issued from thesensor apparatus 100 is outputted to the external measuring equipmentvia the terminal 6.

(Intermediate Cover Member 1A)

In this embodiment, as shown in FIG. 1B, the intermediate cover member1A is placed in juxtaposition to the detecting element 3 on the uppersurface of the first cover member 1. Moreover, as shown in FIGS. 1A and3C, the intermediate cover member 1A and the detecting element 3 arearranged with a spacing. Note that the intermediate cover member 1A andthe detecting element 3 may be arranged with their sides kept in contactwith each other.

As shown in FIGS. 1B and 2B, the intermediate cover member 1A has theform of a flat frame constructed of a flat plate having a recess-formingarea 4, and, the thickness of the intermediate cover member 1A falls inthe range of 0.1 mm to 0.5 mm, for example.

In this embodiment, as shown in FIG. 1B, the recess-forming area 4 is anarea located downstream of a first upstream portion 1Aa. Theintermediate cover member 1A is joined to the flat plate-shaped firstcover member 1, whereupon an element placement section 5 is defined bythe first cover member 1 and the intermediate cover member 1A. That is,the upper surface of the first cover member 1 located inside therecess-forming area 4 becomes the bottom surface of the elementplacement section 5, and, the inner wall of the recess-forming area 4becomes the inner wall of the element placement section 5.

As shown in FIGS. 1A to 1C and 3A to 3E, in a region located downstreamof the detecting element 3, the intermediate cover member 1A does notexist on the first cover member 1. This makes it possible to inhibit orreduce generation of bubbles in a part of the intermediate cover member1A located downstream of the first upstream portion 1Aa. In consequence,an analyte liquid can be delivered in a bubble-free state onto thedetecting element 3, thus achieving an improvement in sensitivity oraccuracy in detection.

As the material for forming the intermediate cover member 1A, forexample, resin (including plastics), paper, non-woven fabric, and glasscan be used. More specifically, resin materials such as polyester resin,polyethylene resin, acrylic resin, and silicone resin are desirable foruse. The first cover member 1 and the intermediate cover member 1A maybe formed of either the same material or different materials.

Moreover, in this embodiment, the intermediate cover member 1A includesthe first upstream portion 1Aa. As shown in FIGS. 1A and 1B, when viewedfrom above, the detecting element 3 is located on the downstream siderelative to the first upstream portion 1Aa. In this case, when ananalyte liquid flows out over the detecting element 3 after passingthrough a part of the flow channel 15 which corresponds to the firstupstream portion 1Aa, an excess of the analyte liquid over an amount ofthe analyte liquid required for measurement flows downstream, whereforean adequate amount of the analyte liquid can be fed to the detectingelement 3.

(Second Cover Member 2)

As shown in FIGS. 1B and 3E, the second cover member 2 covers thedetecting element 3, and is joined to the first cover member 1 and theintermediate cover member 1A. As shown in FIGS. 1B and 1C, the secondcover member 2 comprises a third substrate 2 a and a fourth substrate 2b.

As the material for forming the second cover member 2, for example,resin (including plastics), paper, non-woven fabric, and glass can beused. More specifically, resin materials such as polyester resin,polyethylene resin, acrylic resin, and silicone resin are desirable foruse. The first cover member 1 and the second cover member 2 may beformed of the same material. In this case, deformation resulting fromthe difference in thermal expansion coefficient between the first andsecond cover members can be minimized. The second cover member 2 mayeither be joined only to the intermediate cover member 1A or be joinedto both of the first cover member 1 and the intermediate cover member1A.

As shown in FIGS. 1C, 3C, and 3D, the third substrate 2 a is bonded tothe upper surface of the intermediate cover member 1A. The thirdsubstrate 2 a is shaped like a flat plate having a thickness of 0.1 mmto 0.5 mm, for example. The fourth substrate 2 b is bonded to the uppersurface of the third substrate 2 a. The fourth substrate 2 b is shapedlike a flat plate having a thickness of 0.1 mm to 0.5 mm, for example.By joining the fourth substrate 2 b to the third substrate 2 a, as shownin FIG. 1B, the flow channel 15 is formed on the lower surface of thesecond cover member 2. The flow channel 15 extends from the inlet port14 to at least a region immediately above the reaction section 13, andhas a rectangular sectional profile, for example. The third substrate 2a and the fourth substrate 2 b may be formed of the same material, or,an unitary construction of the combined third and fourth substrates 2 aand 2 b may be used.

In this embodiment, as shown in FIG. 1B, neither the intermediate covermember 1A nor the third substrate 2 a exists at an end of the flowchannel 15, and, a gap left between the fourth substrate 2 b and thefirst cover member 1 serves as an air release hole 18. The air releasehole 18 is provided to let air and so forth present in the flow channel15 go out. The opening of the air release hole 18 may be given any shapewhich is capable of release of air present in the flow channel 15, andthus, for example, a circular shape or a rectangular shape may beadopted. For example, a circular air release hole 18 is designed to havea diameter of less than or equal to 2 mm, and, a rectangular air releasehole 18 is designed so that each side of it has a length of less than orequal to 2 mm.

The first cover member 1, the intermediate cover member 1A, and thesecond cover member 2 may be formed of the same material. In this case,since these members are substantially uniform in thermal expansioncoefficient, it is possible to reduce deformation of the sensorapparatus 100 caused by the difference in thermal expansion coefficientamong the members. Moreover, in the case of application of a biomaterialto the reaction section 13, some biomaterials are prone to qualitydegradation under external light such as ultraviolet rays. In thisregard, it is advisable to use an opaque material having light-blockingcapability as the material for forming the first cover member 1, theintermediate cover member 1A, and the second cover member 2. On theother hand, when the reaction section 13 is substantially free ofexternal light-induced quality degradation, the second cover member 2constituting the flow channel 15 may be formed of a nearly transparentmaterial. In this case, the condition of an analyte liquid flowingthrough the interior of the flow channel 15 can be visually checked,thus permitting the combined use of an optical detection system.

(Detecting Element 3)

The detecting element 3 in the present embodiment will be described withreference to FIGS. 1A to 6B, in particular, FIGS. 4 to 6B.

As shown in FIGS. 6A and 6B, the detecting element 3 generally comprisesan element substrate 10 a disposed on the upper surface of the firstcover member 1, and at least one detecting section 10 b, disposed on theupper surface of the element substrate 10 a, for detecting an object tobe detected (detection target) contained in an analyte liquid.

More specifically, the detecting element 3 in the present embodimentcomprises: the element substrate 10 a; the detecting section 10 bdisposed on the upper surface of the element substrate 10 a, thedetecting section 10 b including the reaction section 13 having animmobilization film 13 a to detect an object to be detected, a first IDT(InterDigital Transducer) electrode 11 configured to generate anacoustic wave which propagates toward the reaction section 13, and asecond IDT electrode 12 configured to receive the acoustic wave whichhas passed through the reaction section 13; and a protective film 28which covers the first IDT electrode 11 and the second IDT electrode 12.The upper surface of the element substrate 10 a is configured so that aregion 10 a 2 thereof where the reaction section 13 is located is at alower level than regions 10 a 1 thereof where the first IDT electrode 11and the second IDT electrode 12 are located. The detecting section 10 bincludes, in addition to the first IDT electrode 11, the reactionsection 13, and the second IDT electrode 12, the protective film 28, afirst extraction electrode 19, a second extraction electrode 20, and soforth. The protective film 28 may be given any shape which is capable ofcovering the first IDT electrode 11 and the second IDT electrode 12without limitation. For example, the protective film 28 may cover aregion extending from the first IDT electrode 11 to the second IDTelectrode 12, or discretely cover the first IDT electrode 11 and thesecond IDT electrode 12.

(Element Substrate 10 a)

The element substrate 10 a is constructed of a substrate of singlecrystal having piezoelectric properties such for example as quartz,lithium tantalate (LiTaO₃) single crystal, or lithium niobate (LiNbO₃)single crystal. The planar configuration and dimensions of the elementsubstrate 10 a are suitably determined. The element substrate 10 a has athickness of 0.3 mm to 1 mm, for example.

In this embodiment, as described above, as shown in FIGS. 6A and 6B, theupper surface of the element substrate 10 a is configured so that theregion 10 a 2 where the reaction section 13 is located is at a lowerlevel than the regions 10 a 1 where the first IDT electrode 11 and thesecond IDT electrode 12 are located. In this case, in the reactionsection 13, energy of SAW (Surface Acoustic Wave) propagating betweenthe first IDT electrode 11 and the second IDT electrode 12 is readilyconcentrated on the immobilization film 13 a, wherefore an object to bedetected contained in an analyte liquid can be detected with highsensitivity. In the upper surface of the element substrate 10 a, giventhat the wavelength of SAW propagating between the first IDT electrode11 and the second IDT electrode 12 is λ, then the region 10 a 2 wherethe reaction section 13 is located is 0.02λ or below lower than theregions 10 a 1 where the first IDT electrode 11 and the second IDTelectrode 12 are located.

The upper surface of the element substrate 10 a is configured so that asurface roughness of the region 10 a 2 where the reaction section 13 islocated is greater than a surface roughness of the regions 10 a 1 wherethe first IDT electrode 11 and the second IDT electrode 12 are located.In this case, in the reaction section 13, aptamers, antibodies, etc.,which will hereafter be described, can be immobilized at high densities,thus achieving an improvement in detection sensitivity. The surfaceroughness of each constituent element is determined by measurement usingarithmetic average roughness Ra. In the case where a film such as anelectrode or the like is disposed on the upper surface, which is ameasurement target, of the element, for example, graphic analyses of thesectional profile of the upper surface are performed on the basis of aphotograph of the section obtained by means of SEM (Scanning ElectronMicroscopy), TEM (Transmission Electron Microscopy), or otherwise, forsurface roughness measurement. Moreover, when direct measurement of theupper surface which is a measurement target is possible, the measurementis effected with use of a commonly-used surface-roughness meter ofcontact type or non-contact type. The conditions described hold in whatfollows unless otherwise specified.

A surface roughness of a region of the element substrate 10 a where theimmobilization film 13 a is located is greater than a surface roughnessof the upper surface of the immobilization film 13 a. This makes itpossible to increase the strength of adhesion between the elementsubstrate 10 a and the immobilization film 13 a, as well as toimmobilize aptamers, antibodies, etc. onto the immobilization film 13 aat high densities, and thereby achieve an improvement in detectionsensitivity.

(IDT El 11 and 12)

As shown in FIGS. 4, 6A and 6B, the first IDT electrode 11 comprises apair of comb electrodes. Each comb electrode includes two bus barsopposed to each other and a plurality of electrode fingers 11 a to 11 e(11 a, 11 b, 11 c, 11 d) each extending from corresponding one of thebus bars toward the other. A pair of the comb electrodes is disposed sothat the plurality of electrode fingers 11 a to 11 e are arranged in aninterdigitated pattern. The second IDT electrode 12 is similar inconfiguration to the first IDT electrode 11. The first IDT electrode 11and the second IDT electrode 12 constitute a transversal IDT electrode.

The first IDT electrode 11 is intended for generation of predeterminedSAW, and the second IDT electrode 12 is intended for reception of theSAW generated in the first IDT electrode 11. The first IDT electrode 11and the second IDT electrode 12 are positioned on the same straight lineso that the SAW generated in the first IDT electrode 11 can be receivedby the second IDT electrode 12. Frequency response characteristics canbe designed on the basis of the number of the electrode fingers of thefirst IDT electrode 11 and the second IDT electrode 12, the distancebetween the adjacent electrode fingers, the crossing width of theelectrode fingers, etc., used as parameters.

There are various modes of vibration for SAW to be excited by the IDTelectrode. In the detecting element 3 according to the embodiment, forexample, a vibration mode of transversal waves called SH waves isutilized. The frequency of SAW may be set within the range of severalmegahertz (MHz) to several gigahertz (GHz), for example. It is advisableto set the SAW frequency within the range of several hundred MHz to 2GHz from the practicality standpoint, and also in the interest ofminiaturization of the detecting element 3 that will eventually beconducive to miniaturization of the sensor apparatus 100. Thethicknesses and lengths of predetermined constituent elements in theembodiment will be described with respect to the case where the centerfrequency of SAW falls in a several hundred MHz range.

The first IDT electrode 11 and the second IDT electrode 12 may be of asingle-layer structure composed of, for example, a gold thin layer, ormay be of a multilayer structure such as a three-layer structurecomposed of a titanium layer, a gold layer, and a titanium layer, or athree-layer structure composed of a chromium layer, a gold layer, and achromium layer, in the order named, from the element-substrate 10 aside.

A thickness of the first IDT electrode 11 and the second IDT electrode12 may be set to fall within the range of 0.005λ to 0.015λ, for example.

An elastic member may be disposed externally of the first IDT electrode11 and the second IDT electrode 12 in a SAW propagation direction (widthdirection) to reduce SAW reflection.

(Reaction Section 13)

As shown in FIGS. 4, 6A and 6B, the reaction section 13 is disposedbetween the first IDT electrode 11 and the second IDT electrode 12.

In this embodiment, the reaction section 13 comprises the immobilizationfilm 13 a (for example, a metallic film) formed on the upper surface ofthe element substrate 10 a, and a reactant immobilized on the uppersurface of the immobilization film 13 a for reaction with an object tobe detected. The reactant is suitably selected depending on an object tobe detected which is a detection target. For example, when the object tobe detected is a specific cell or living tissue present in an analyteliquid, an aptamer composed of a nucleic acid or a peptide can be usedas the reactant. For example, in this embodiment, while a reactionbetween the reactant and the object to be detected may be a bindingreaction of the object to be detected and the reactant such as achemical reaction or an antigen-antibody reaction, the reaction is notso limited, but may be a binding reaction of the object to be detectedand the reactant under the interaction of the object to be detected withthe reactant, or an adsorption reaction of the object to be detected tothe reactant. Exemplary of a reactant which can be used for the reactionsection 13 in the embodiment is one which causes, by its presence,variation in surface-acoustic-wave characteristics according to the typeor content of the object to be detected when an analyte is brought intocontact with the reaction section 13. The reaction section 13 isintended for reaction with an object to be detected contained in ananalyte liquid, and, more specifically, upon contact of an analyteliquid with the reaction section 13, a specific object to be detectedcontained in the analyte liquid is bound to an aptamer adapted to theobject to be detected.

The immobilization film 13 a (metallic film) may be of a single-layerstructure composed of, for example, a gold layer, or may be of amultilayer structure such as a two-layer structure composed of atitanium layer and a gold layer situated on the titanium layer or atwo-layer structure composed of a chromium layer and a gold layersituated on the chromium layer. Moreover, the immobilization film 13 amay be formed of the same material as a material used for the first IDTelectrode 11 and the second IDT electrode 12. In this case, theimmobilization film 13 a and the first and second IDT electrodes 11 and12 can be formed in the same process step. Instead of theabove-mentioned metallic film, for example, an oxide film such as a SiO₂film or TiO₂ film may be used as the material of construction of theimmobilization film 13 a.

Given that the first IDT electrode 11, the second IDT electrode 12, andthe reaction section 13 arranged in the width direction of the flowchannel are grouped into a set, then, as shown in FIG. 4 , two sets areprovided in the sensor apparatus 100 according to the embodiment. Inthis case, by designing the reaction section 13 of one of the sets andthe reaction section 13 of the other to undergo reaction with differentobjects to be detected, it is possible to detect two different objectsto be detected by a single sensor apparatus.

In this embodiment, as shown in FIG. 6B, the upper surface of theimmobilization film 13 a is positioned at a higher level than at leastone of the regions 10 a 1 of the upper surface of the element substrate10 a where the first IDT electrode 11 and the second IDT electrode 12are located, respectively. In this case, in the reaction section 13,energy of SAW propagating between the first IDT electrode 11 and thesecond IDT electrode 12 is readily concentrated on the upper surface ofthe immobilization film 13 a, wherefore an object to be detected can bedetected with higher sensitivity.

Moreover, as shown in FIG. 6B, the upper surface of the immobilizationfilm 13 a is positioned at a lower level than at least one of the uppersurface of the first IDT electrode 11 and the upper surface of thesecond IDT electrode 12. In this case, in the reaction section 13,energy of SAW propagating between the first IDT electrode 11 and thesecond IDT electrode 12 is readily concentrated on the upper surface ofthe immobilization film 13 a, wherefore an object to be detected can bedetected with higher sensitivity.

A thickness of the immobilization film 13 a may be set to fall withinthe range of 0.005λ to 0.015λ, for example. In this embodiment, as shownin FIG. 6B, the thickness of the immobilization film 13 a is smallerthan at least one of the thickness of the first IDT electrode 11 and thethickness of the second IDT electrode 12. In this case, even if theimmobilization film 13 a has a relatively small thickness, in thereaction section 13, losses of energy of SAW propagating between thefirst IDT electrode 11 and the second IDT electrode 12 can be reduced.In addition to that, since the SAW energy is readily concentrated on theupper surface of the immobilization film 13 a, it is possible to detectan object to be detected with higher sensitivity.

The surface roughness of the upper surface of the immobilization film 13a is greater than at least one of the surface roughness of the uppersurface of the first IDT electrode 11 and the surface roughness of theupper surface of the second IDT electrode 12. In this case, in thereaction section 13, since an increase in surface area can be achieved,it is possible to immobilize aptamers, antibodies, etc. at highdensities, and thereby improve the detection sensitivity even further.The surface roughness of the upper surface of the immobilization film 13a, which falls in the range of, for example, 0.5 to 2.0 nm in terms ofRa, may be obtained by measuring the upper surface, as a measurementtarget, using a commonly-used surface-roughness meter of contact type ornon-contact type. Moreover, the surface roughness of the upper surfaceof each of the first IDT electrode 11 and the second IDT electrode 12may be obtained by measuring the upper surface, as a measurement target,of either any of comb electrode portions or a portion connecting theseelectrode portions using a commonly-used surface-roughness meter ofcontact type or non-contact type.

(Protective Film 28)

As shown in FIGS. 6A and 6B, the protective film 28 covers the first IDTelectrode 11 and the second IDT electrode 12. This makes it possible toinhibit an analyte liquid from contact with the first IDT electrode 11and the second IDT electrode 12, and thereby retard corrosion of the IDTelectrodes caused by oxidation, for example. Examples of materials usedfor the protective film 28 include silicon oxide, aluminum oxide, zincoxide, titanium oxide, silicon nitride, and silicon. Such a material isproperly used as a major constituent, namely a component constitutingthe greatest proportion in mass, of the protective film 28-formingmaterial, and is therefore not defined as the constituent material whenmixed as impurities in very small amounts.

In this embodiment, as shown in FIG. 6B, the protective film 28 liesalso in between the reaction section 13 and at least one of the firstIDT electrode 11 and the second IDT electrode 12. This interposedportion 28 a makes it possible to inhibit or reduce contact of the sideof the IDT electrode with an analyte liquid. In this construction, asshown in FIG. 6B, the protective film 28 is located without contact withand apart from the reaction section 13. This helps reduce the influenceof the protective film 28 upon the sensitivity of the reaction section13 to SAW.

Moreover, as shown in FIG. 6B, the protective film 28 is configured sothat, when viewed in a lateral section thereof, a lower end part of anend located on the reaction section 13 side of the protective film 28 iscloser to the reaction section 13 than an upper end part of the endpart. As used herein, the language “lateral section” means, as will beseen from FIG. 1B for example, a section taken along the line a-a ofFIG. 1A or a line perpendicular to the line a-a, looking from the sideof the sensor apparatus. Moreover, the language “end located on thereaction section 13 side” means an end of the protective film 28opposite the end of at least one of the first IDT electrode 11 and thesecond IDT electrode 12 under the condition where, for example, asdescribed above, the protective film 28 lies also in between thereaction section 13 and at least one of the first IDT electrode 11 andthe second IDT electrode 12, and does not cover the entire area of thereaction section 13. Furthermore, as shown in FIG. 6B, in the protectivefilm 28 as viewed in a lateral section, the end located on the reactionsection 13 side is inclined so that the distance between the end and thereaction section 13 becomes shorter gradually from the upper end part tothe lower end part. This makes it possible to inhibit an analyte liquidfrom contact with the first IDT electrode 11 and the second IDTelectrode 12 more effectively. Moreover, by forming the protective film28 so as to cover the upper surface of the element substrate 10 a, it ispossible to enhance stability of connection with the element substrate10 a.

In this embodiment, a thickness of the protective film 28 may be set tofall within the range of 0.001λ to 0.05λ, for example. While thethickness of the protective film 28 may be defined as the distance fromthe upper surface of the element substrate 10 a to the upper surface ofthe protective film 28 as measured in a part of the protective film 28which covers neither the first IDT electrode 11 nor the second IDTelectrode 12, the measurement in other part will not be excluded herein.

A thickness of the protective film 28 may be set to be smaller than atleast one of the thickness of the first IDT electrode 11 and thethickness of the second IDT electrode 12. This makes it possible toreduce the influence of the protective film 28 upon SAW propagatingbetween the first IDT electrode 11 and the second IDT electrode 12, andthereby reduce losses of SAW energy. In this case, the upper surface ofthe protective film 28 may be, at least partly, positioned at a lowerlevel than at least one of the upper surface of the first IDT electrode11 and the upper surface of the second IDT electrode 12.

As shown in FIGS. 4, 6A and 6B, the first IDT electrode 11 and thesecond IDT electrode 12 include the plurality of electrode fingers 11 ato 11 e which are spaced apart from each other and a plurality ofelectrode fingers 12 a to 12 e (12 a, 12 b, 12 c, 12 d, and 12 e) whichare spaced apart from each other, respectively, and, as shown in FIG.6B, the protective film 28 is made in continuous (connected) form so asto lie over two adjacent electrode fingers, for example, the electrodefingers 11 a and 11 b, as well as 12 a and 12 b of the plurality ofelectrode fingers 11 a to 11 e, as well as 12 a to 12 e, and also over apart of the element substrate 10 a which is exposed between the twoadjacent electrode fingers 11 a and 11 b, as well as 12 a and 12 b. Thismakes it possible to inhibit occurrence of short-circuiting between theplurality of electrode fingers of the IDT electrode caused by an analyteliquid.

(Extraction Electrodes 19 and 20)

As shown in FIG. 4 , the first extraction electrode 19 is connected tothe first IDT electrode 11, and the second extraction electrode 20 isconnected to the second IDT electrode 12. The first extraction electrode19 is extracted from the first IDT electrode 11 in the oppositedirection to the reaction section 13, and, an end 19 e of the firstextraction electrode 19 is electrically connected to the wiring line 7disposed in the first cover member 1. The second extraction electrode 20is extracted drawn from the second IDT electrode 12 in the oppositedirection to the reaction section 13, and, an end 20 e of the secondextraction electrode 20 is electrically connected to the wiring line 7.

The first extraction electrode 19 and the second extraction electrode 20may be made similar in material and configuration to the first IDTelectrode 11 and the second IDT electrode 12, and may thus be of asingle-layer structure composed of, for example, a gold thin layer, ormay be of a multilayer structure such as a three-layer structurecomposed of a titanium layer, a gold layer, and a titanium layer, or athree-layer structure composed of a chromium layer, a gold layer, and achromium layer, in the order named, from the element-substrate 10 aside.

(Detection of Object to be Detected Using Detecting Element 3)

In the process of detection of an object to be detected contained in ananalyte liquid by the detecting element 3 that utilizes SAW as abovedescribed, the first step is to apply a predetermined voltage fromexternal measuring equipment to the first IDT electrode 11 via thewiring line 7, the first extraction electrode 19, and so forth.

Upon the voltage application, on the surface of the element substrate 10a, the first IDT electrode 11-forming region 10 a 1 is excited, thusproducing SAW having a predetermined frequency. Part of the SAW sogenerated propagates toward the reaction section 13, passes through thereaction section 13, and reaches the second IDT electrode 12. In thereaction section 13, the aptamer on the reaction section 13 is bound toa specific object to be detected contained in the analyte liquid undermutual reaction, and the weight (mass) of the reaction section 13changes correspondingly, which results in variation in thecharacteristics, such as a phase, of the SAW passing through thereaction section 13. In response to the arrival of the SAW having variedcharacteristics at the second IDT electrode 12, a corresponding voltageis developed in the second IDT electrode 12.

The thereby developed voltage is outputted through the second extractionelectrode 20, the wiring line 70, and so forth. By reading the outputwith external measuring equipment, it is possible to examine theproperties and constituents of the analyte liquid containing the objectto be detected.

In the sensor apparatus 100, capillarity is utilized to direct theanalyte liquid to the reaction section 13.

Specifically, as described earlier, when the second cover member 2 isjoined to the intermediate cover member 1A, as shown in FIGS. 1A to 1C,the flow channel 15 is defined, in the form of a narrow elongate pipe,on the lower surface of the second cover member 2. Thus, by setting, forexample, the width or the diameter of the flow channel 15 at apredetermined value with consideration given to the type of the analyteliquid, the materials of construction of the intermediate cover member1A and the second cover member 2, and so forth, it is possible to causecapillarity in the flow channel 15 in the form of a narrow elongatepipe. For example, the flow channel 15 has a width of 0.5 mm to 3 mm,and a depth of 0.1 mm to 0.5 mm. As shown in FIG. 1B, the flow channel15 has a downstream portion (extension) 15 b which is a portionextending beyond the reaction section 13, and, the second cover member 2is formed with the air release hole 18 which is in communication withthe extension 15 b. Upon admission of the analyte liquid into the flowchannel 15, air present in the flow channel 15 is expelled out of theair release hole 18.

With such a pipe form capable of causing capillarity defined by thecover members including the intermediate cover member 1A and the secondcover member 2, upon contact with the inlet port 14, the analyte liquidis drawn into the interior of the sensor apparatus 100 while passingthrough the flow channel 15. Thus, the sensor apparatus 100 has ananalyte liquid suction mechanism built in itself, and is thereforecapable of analyte liquid suction without using an instrument such as apipette.

(Positional Relationship Between Flow Channel 15 and Detecting Element3)

In this embodiment, while the analyte-liquid flow channel 15 has a depthof about 0.3 mm, the detecting element 3 has a thickness of about 0.3mm, that is; as shown in FIG. 1B, the depth of the flow channel 15 andthe thickness of the detecting element 3 are substantially equal.Therefore, if the detecting element 3 is placed as it is on the uppersurface of the first cover member 1, the flow channel 15 will beblocked. In this regard, in the sensor apparatus 100, as shown in FIGS.1B and 5 , the element placement section 5 is defined by the first covermember 1 on which the detecting element 3 is mounted, and theintermediate cover member 1A joined onto the first cover member 1. Thedetecting element 3 is housed in this element placement section 5 sothat the analyte-liquid flow channel 15 will not be blocked. That is,the depth of the element placement section 5 is adjusted to besubstantially equal to the thickness of the detecting element 3, and,the detecting element 3 is mounted inside the element placement section5. Thereby, the flow channel 15 can be provided.

The detecting element 3 is secured to the bottom surface of the elementplacement section 5 by, for example, a die-bonding material composedpredominantly of resin such as epoxy resin, polyimide resin, or siliconeresin.

The end 19 e of the first extraction electrode 19 and the wiring line 7are electrically connected to each other by a metallic narrow wire 27formed of, for example, Au. The connection between the end 20 e of thesecond extraction electrode 20 and the wiring line 7 is made in asimilar way. Means for connecting the wiring line 7 with the first andsecond extraction electrodes 19 and 20 is not limited to the metallicnarrow wire 27, but may be of an electrically-conductive adhesive suchas a Ag paste. Since a gap is left in the part where the wiring line 7makes connection with each of the first and second extraction electrodes19 and 20, it is possible to suppress damage of the metallic narrow wire27 when bonding the second cover member 2 to the first cover member 1.Moreover, the first extraction electrode 19, the second extractionelectrode 20, the metallic narrow wire 27, and the wiring line 7 arecovered with the protective film 28. By covering the first extractionelectrode 19, the second extraction electrode 20, the metallic narrowwire 27, and the wiring line 7 with the protective film 28, it ispossible to suppress corrosion of these electrodes and the like.

As described heretofore, according to the sensor apparatus 100 in theembodiment, by placing the detecting element 3 in the element placementsection 5 of the first cover member 1, it is possible to provide theanalyte-liquid flow channel 15 extending from the inlet port 14 to thereaction section 13, and thereby allow the analyte liquid, which hasbeen drawn into the apparatus through the inlet port 14 undercapillarity for example, to flow to the reaction section 13. That is,even with use of the detecting element 3 having a certain thickness,since the sensor apparatus 100 has an analyte liquid suction mechanismbuilt in itself, it is possible to provide a sensor apparatus 100capable of directing an analyte liquid to the detecting element 3efficiently.

<Manufacturing Process of Detecting Element>

The following describes a procedure in the making of the detectingelement 3 provided in the sensor apparatus 100 according to theembodiment of the invention. FIGS. 7A to 7J are schematic views showingprocedural steps for manufacturing the detecting element 3.

First, a quartz-made element substrate 10 a is washed. After that, on anas needed basis, an Al film is formed on the lower surface of theelement substrate 10 a by RF sputtering technique (FIG. 7A).

Next, an electrode pattern is formed on the upper surface of the elementsubstrate 10 a. In this step, a photoresist pattern 51 of image reversaltype for electrode-pattern formation is formed by photolithographytechnique (FIG. 7B).

Next, a metallic layer 52 having a three-layer structure composed ofTi/Au/Ti layers is formed on each of a photoresist-bearing part and aphotoresist-free part of the upper surface of the element substrate 10 aby electron-beam vapor deposition equipment (FIG. 7C).

Next, a Ti/Au/Ti electrode pattern 53 is formed by lifting off thephotoresist pattern 51 using a solvent, followed by oxygen-plasma ashingtreatment (FIG. 7D). In this embodiment, the Ti/Au/Ti electrode pattern53 constitutes, in addition to a pair of IDT electrodes 11 and 12, areflector and mounting extraction electrodes 19 and 20. The pair of IDTelectrodes 11 and 12 are disposed so as to face each other, and, one ofthem serves as a transmitter, whereas the other serves as a receiver.

Next, a protective film 28 is formed on the upper surface of the elementsubstrate 10 a so as to cover the Ti/Au/Ti electrode pattern by, forexample, TEOS (Tetra Ethyl Ortho Silicate)-plasma CVD technique (FIG.7E).

Next, a protective film 28 pattern is formed by forming a positivephotoresist 54 on the upper surface of the protective film 28, followedby etching of the protective film 28 using RIE equipment (FIG. 7F). Atthis time, the protective film 28 is overetched at its areacorresponding to the center of the element substrate 10 a where animmobilization film 13 a is to be formed, thus forming a recessed areawhich is lower in level than nearby area. After that, the photoresist 54is lifted off with use of a solvent, whereupon the protective film 28pattern is formed so as to cover the IDT electrodes 11 and 12.

Next, a photoresist pattern 55 for immobilization-film 13 a formation isformed by photolithography technique, and a metallic layer having atwo-layer structure composed of Au/Ti layers, which becomes a reactionsection 13, is formed by electron-beam vapor deposition equipment (FIG.7G). Following the lifting-off of the photoresist pattern 55 using asolvent, oxygen-plasma ashing treatment is performed, whereupon theimmobilization film 13 a having a two-layer structure composed of Au/Tilayers is formed so as to lie between the paired IDT electrodes 11 and12 (FIG. 7H). Given that the pair of IDT electrodes 11 and 12 and theAu/Ti immobilization film 13 a are grouped into a set, then two sets areprovided on a single sensor. One of the two sets is used as a set fordetection, whereas the other is used as a set for reference. After that,the Al film 50 formed on the lower surface of the element substrate 10 ais removed with use of fluonitric acid.

An aptamer composed of a nucleic acid or a peptide is immobilized on theupper surface of the immobilization film 13 a to form the reactionsection 13.

In the manner as described heretofore, the detecting element 3 isformed.

Next, the element substrate 10 a is cut in a predetermined size bydicing (FIG. 7I). After that, separate detecting elements 3 obtained bycutting process are fixedly attached, at their back sides, onto a glassepoxy mounting substrate having a wiring formed thereon in advance(hereafter referred to as “mounting substrate”) which is equivalent tothe first cover member 1, with use of an epoxy adhesive. Then, a Aunarrow wire used as the lead wire 27 is set to provide electricalconnection between the wiring line 7 connected to each of the terminals6 disposed on the mounting substrate and each of the ends 19 e and 20 eof the extraction electrodes disposed on the detecting element 3 (FIG.7J).

Following the completion of placement of the intermediate cover member1A, the second cover member 2, and so forth, the sensor apparatus 100 isformed.

The manufacturing process of the detecting element 3, as well as themanufacturing process of the sensor apparatus 100, is not limited to theaforestated procedure shown in FIGS. 7A to 7J, and it is thus possibleto adopt any other manufacturing process that enables production of theelement substrate 10 a whose upper surface is configured so that theregion 10 a 2 where the reaction section 13 is located is lower than theregions 10 a 1 where the first IDT electrode 11 and the second IDTelectrode 12 are located.

The invention is not limited to the embodiment thus far described, andmay therefore be carried into effect in various forms.

Although the reaction section 13 in the aforestated embodiment has beenillustrated as comprising the immobilization film 13 a and the aptamerimmobilized on the upper surface of the immobilization film 13 a, theinvention is not limited to the aptamer, and thus, as an alternative, areactant which undergoes reaction with a object to be detected containedin an analyte liquid and causes variation in SAW characteristics beforeand after analyte passage through the reaction section 13 may beimmobilized on the upper surface of the immobilization film 13 a.Moreover, for example, in the case where the object to be detected inthe analyte liquid reacts with the immobilization film 13 a, thereaction section 13 may be composed solely of the immobilization film 13a without using a reactant such as the aptamer. In addition, thereaction section 13 may be defined by a region between the first IDTelectrode 11 and the second IDT electrode 12 on the surface of theelement substrate 10 a constructed of a piezoelectric substrate withoutusing the immobilization film 13 a. In this case, an analyte liquid isapplied directly to the surface of the element substrate 10 a to detectthe physical properties, such as the viscosity, of the analyte liquid.More specifically, SAW phase variation resulting from a change in, forexample, the viscosity of the analyte liquid on the reaction section 13is monitored. Moreover, the aptamer may be immobilized on the uppersurface of a non-conductive film which is used as the immobilizationfilm 13 a instead of a metallic film.

Moreover, the detecting element 3 may be constructed of a singlesubstrate on which a variety of devices are disposed. For example, anenzyme electrode for use with enzyme electrode method may be disposednext to a SAW device. In this case, in addition to measurement based onthe immuno method using an antibody or aptamer, measurement based on theenzymatic method can also be conducted, thus increasing the number ofmeasurement points that can be checked at one time.

Moreover, while the embodiment has been described with respect to thecase of providing a single detecting element 3, a plurality of detectingelements 3 may be provided. In this case, the element placement section5 is formed for each detecting element 3 on an individual basis, or, theelement placement section 5 is configured to have a length or widthlarge enough to receive all of the detecting elements 3.

Moreover, while the embodiment has been described with respect to thecase where the first cover member 1, the intermediate cover member 1A,and the second cover member 2 are provided as separate components, thisdoes not constitute any limitation, and thus either a combination ofsome of these members in an unitary structure or a combination of allthe members in an unitary structure may be adopted.

REFERENCE SIGNS LIST

-   -   1: First cover member    -   1A: Intermediate cover member    -   1Aa: First upstream portion    -   2: Second cover member    -   2 a: Third substrate    -   2 b: Fourth substrate    -   3: Detecting element    -   4: Recess-forming area    -   5: Element placement section    -   6: Terminal    -   7: Wiring line    -   9: Filler member    -   10 a: Element substrate    -   10 b: Detecting section    -   11: First IDT electrode    -   12: Second IDT electrode    -   13: Reaction section    -   13 a: Immobilization film    -   14: Inlet port    -   15: Flow channel    -   15 a: Upstream portion    -   15 b: Downstream portion (extension)    -   18: Air release hole    -   19: First extraction electrode    -   19 e: End    -   20: Second extraction electrode    -   20 e: End    -   27: Lead wire (metallic narrow wire)    -   28: Protective film    -   100: Sensor apparatus

The invention claimed is:
 1. A sensor apparatus, comprising: an elementsubstrate comprising a first top surface, a second top surface and athird top surface; an immobilization film disposed on the first topsurface wherein the immobilization film has a single top surface, afirst IDT electrode disposed on the second top surface, and a second IDTelectrode disposed on the third top surface of the element substrate;wherein the immobilization film disposed is between the first IDTelectrode and the second IDT electrode, and an entirety of the singletop surface of the immobilization film is positioned at a lower levelthan at least one of an upper surface of the first IDT electrode and anupper surface of the second IDT electrode.
 2. The sensor apparatusaccording to claim 1, further comprising, a protective film which coversthe first IDT electrode and the second IDT electrode.
 3. The sensorapparatus according to claim 2, wherein the protective film is spacedaway from the immobilization film.
 4. The sensor apparatus according toclaim 2, wherein the protective film is located between theimmobilization film and at least one of the first IDT electrode and thesecond IDT electrode.
 5. The sensor apparatus according to claim 1,further comprising, a reactant located on the immobilization film. 6.The sensor apparatus according to claim 1, wherein a surface roughnessof the single top surface of the immobilization film is greater than atleast one of a surface roughness of the upper surface of the first IDTelectrode and a surface roughness of the upper surface of the second IDTelectrode.
 7. The sensor apparatus according to claim 1, wherein athickness of the immobilization film is smaller than at least one of athickness of the first IDT electrode and a thickness of the second IDTelectrode.
 8. The sensor apparatus according to claim 1, wherein theentirety of the single top surface of immobilization film is at a higherlevel than at least one of the second top surface and the third topsurface.